Antimicrobial Susceptibility of Pseudomonas aeruginosa Is Improved by Pharmacist's Intervention in the Use of Antimicrobial Agents

2012 ◽  
Vol 27 (4) ◽  
pp. 285-291
Author(s):  
Masami TSUGITA
mSphere ◽  
2018 ◽  
Vol 3 (2) ◽  
Author(s):  
Xuan Qin ◽  
Chuan Zhou ◽  
Danielle M. Zerr ◽  
Amanda Adler ◽  
Amin Addetia ◽  
...  

ABSTRACTClinical isolates ofPseudomonas aeruginosafrom patients with cystic fibrosis (CF) are known to differ from those associated with non-CF hosts by colony morphology, drug susceptibility patterns, and genomic hypermutability.Pseudomonas aeruginosaisolates from CF patients have long been recognized for their overall reduced rate of antimicrobial susceptibility, but their intraclonal MIC heterogeneity has long been overlooked. Using two distinct cohorts of clinical strains (n= 224 from 56 CF patients,n= 130 from 68 non-CF patients) isolated in 2013, we demonstrated profound Etest MIC heterogeneity in CFP. aeruginosaisolates in comparison to non-CFP. aeruginosaisolates. On the basis of whole-genome sequencing of 19 CFP. aeruginosaisolates from 9 patients with heterogeneous MICs, the core genome phylogenetic tree confirmed the within-patient CFP. aeruginosaclonal lineage along with considerable coding sequence variability. No extrachromosomal DNA elements or previously characterized antibiotic resistance mutations could account for the wide divergence in antimicrobial MICs betweenP. aeruginosacoisolates, though many heterogeneous mutations in efflux and porin genes and their regulators were present. A unique OprD sequence was conserved among the majority of isolates of CFP. aeruginosaanalyzed, suggesting a pseudomonal response to selective pressure that is common to the isolates. Genomic sequence data also suggested that CF pseudomonal hypermutability was not entirely due to mutations inmutL,mutS, anduvr. We conclude that the net effect of hundreds of adaptive mutations, both shared between clonally related isolate pairs and unshared, accounts for their highly heterogeneous MIC variances. We hypothesize that this heterogeneity is indicative of the pseudomonal syntrophic-like lifestyle under conditions of being “locked” inside a host focal airway environment for prolonged periods.IMPORTANCEPatients with cystic fibrosis endure “chronic focal infections” with a variety of microorganisms. One microorganism,Pseudomonas aeruginosa, adapts to the host and develops resistance to a wide range of antimicrobials. Interestingly, as the infection progresses, multiple isogenic strains ofP. aeruginosaemerge and coexist within the airways of these patients. Despite a common parental origin, the multiple strains ofP. aeruginosadevelop vastly different susceptibility patterns to actively used antimicrobial agents—a phenomenon we define as “heterogeneous MICs.” By sequencing pairs ofP. aeruginosaisolates displaying heterogeneous MICs, we observed widespread isogenic gene lesions in drug transporters, DNA mismatch repair machinery, and many other structural or cellular functions. Coupled with the heterogeneous MICs, these genetic lesions demonstrated a symbiotic response to host selection and suggested evolution of a multicellular syntrophic bacterial lifestyle. Current laboratory standard interpretive criteria do not address the emergence of heterogeneous growth and susceptibilitiesin vitrowith treatment implications.


1970 ◽  
Vol 1 (2) ◽  
pp. 190-194
Author(s):  
Marian W. Wolfe ◽  
Daniel Amsterdam

Plaques similar in appearance to those induced by phage were observed adjacent to chloramphenicol and tetracycline discs on Pseudomonas aeruginosa lawns used for the determination of antibiotic susceptibility. Thirteen strains were selected for study, 10 of which exhibited the plaquing phenomenon. The ability to form plaques induced by tetracycline was not related to any of the biochemical properties of the strains studied, their overall antimicrobial susceptibility pattern, or their pathological source. Some pseudomonad strains were capable of pyocin production; however, the relationship between plaque formation and pyocin production was not apparent. Supernatant fluids of resuspended plaque contents of eight strains originally demonstrating clearings could induce plaques on sensitive indicator lawns only when collected from tetracycline-induced plaque areas; supernatant fluids of the same strains could not produce clearings without previous exposure to the drug. Of the eight supernatant fluids capable of plaque induction, three were active on their homologous indicator lawns. In a subsequent survey of 95 P. aeruginosa strains, it was found that 28 isolates exhibited plaques. Of these, 17 were associated with tetracycline, 7 were associated with chloramphenicol, 3 were associated with triple sulfa; and 1 was associated with nalidixic acid.


2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Emily Roberts

ObjectiveIllustrate how the Utah Department of Health automatically processes antimicrobial susceptibility results that are received electronically.IntroductionThe emerging threat of antimicrobial resistant organisms is a pressing public health concern. Surveillance for antimicrobial resistance can prevent infections, protect patients in the healthcare setting and improve antimicrobial use. In 2018, the Utah Department of Health mandated the reporting of antimicrobial susceptibility panels performed on selected organisms. Utah utilizes the Electronic Message Staging Area (EMSA), a home-grown application to translate, process, and enter electronic laboratory results into UT-NEDSS, Utah’s integrated disease surveillance system. Processing these results electronically is challenging due to the need to interpret results based on the antimicrobial agent combined with the organism it was performed on. The receipt of antimicrobial susceptibility panels has required enhancements to EMSA for these results to be automatically processed.MethodsStand-alone antimicrobial susceptibility LOINCs are configured within EMSA to concatenate during the preprocessing stage. This tells EMSA that when this LOINC is sent within an HL7 message to find the organism name in the corresponding OBR 26.3 (the parent result field). EMSA then creates a new fabricated code that combines the antimicrobial agent with the organism identified from the culture (example: ‘18906-8 Pseudomonas aeruginosa’ is the fabricated code for Ciprofloxacin susceptibility to Pseudomonas aeruginosa).Once these new fabricated antimicrobial susceptibility codes are created, interpretation rules are programmed using current Clinical and Laboratory Standards Institute (CLSI) breakpoints for each unique organism/antimicrobial combination to determine if the result is Susceptible/Intermediate/Resistant. The interpreted test is then run through a set of condition-specific rules to determine how it should be included into UT-NEDSS.ResultsAntimicrobial susceptibility panels performed on Acinetobacter species, Escherichia coli, Klebsiella species, Pseudomonas aeruginosa, Enterobacter species, Candida auris/haemulonii, Mycobacterium tuberculosis, Neisseria gonorrhoeae, Salmonella species, Shigella species, Streptococcus pneumoniae and invasive Staphylococcus aureus are now included in Utah’s Communicable Disease Reporting Rule. Currently, there are 36 antimicrobial agents programmed into EMSA and there are a total of 217 antimicrobial susceptibility codes programmed into the system.ConclusionsProcessing electronic antimicrobial susceptibility results presents unique challenges for processing. Interpretation of results can vary based on test method, performing laboratory, and organism. Enhancing functionality within EMSA was necessary for combining the antimicrobial agent and organism it was performed on. Implementing systems capable of automatically processing complicated antimicrobial susceptibility results should be a priority for any health department interested in expanding their communicable disease rule to include antimicrobial susceptibility testing.


2020 ◽  
Vol 202 (18) ◽  
Author(s):  
Giulia Orazi ◽  
Fabrice Jean-Pierre ◽  
George A. O’Toole

ABSTRACT The thick mucus within the airways of individuals with cystic fibrosis (CF) promotes frequent respiratory infections that are often polymicrobial. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most prevalent pathogens that cause CF pulmonary infections, and both are among the most common etiologic agents of chronic wound infections. Furthermore, the ability of P. aeruginosa and S. aureus to form biofilms promotes the establishment of chronic infections that are often difficult to eradicate using antimicrobial agents. In this study, we found that multiple LasR-regulated exoproducts of P. aeruginosa, including 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), siderophores, phenazines, and rhamnolipids, likely contribute to the ability of P. aeruginosa PA14 to shift S. aureus Newman norfloxacin susceptibility profiles. Here, we observe that exposure to P. aeruginosa exoproducts leads to an increase in intracellular norfloxacin accumulation by S. aureus. We previously showed that P. aeruginosa supernatant dissipates the S. aureus membrane potential, and furthermore, depletion of the S. aureus proton motive force recapitulates the effect of the P. aeruginosa PA14 supernatant on shifting norfloxacin sensitivity profiles of biofilm-grown S. aureus Newman. From these results, we hypothesize that exposure to P. aeruginosa PA14 exoproducts leads to increased uptake of the drug and/or an impaired ability of S. aureus Newman to efflux norfloxacin. Surprisingly, the effect observed here of P. aeruginosa PA14 exoproducts on S. aureus Newman susceptibility to norfloxacin seemed to be specific to these strains and this antibiotic. Our results illustrate that microbially derived products can alter the ability of antimicrobial agents to kill bacterial biofilms. IMPORTANCE Pseudomonas aeruginosa and Staphylococcus aureus are frequently coisolated from multiple infection sites, including the lungs of individuals with cystic fibrosis (CF) and nonhealing diabetic foot ulcers. Coinfection with P. aeruginosa and S. aureus has been shown to produce worse outcomes compared to infection with either organism alone. Furthermore, the ability of these pathogens to form biofilms enables them to cause persistent infection and withstand antimicrobial therapy. In this study, we found that P. aeruginosa-secreted products dramatically increase the ability of the antibiotic norfloxacin to kill S. aureus biofilms. Understanding how interspecies interactions alter the antibiotic susceptibility of bacterial biofilms may inform treatment decisions and inspire the development of new therapeutic strategies.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yong He ◽  
Hang Zhao ◽  
Yuanwen Liu ◽  
He Zhou

AbstractThe worldwide emergence and spread of antimicrobial resistance is accelerated by irrational administration and use of empiric antibiotics. A key point to the crisis is a lack of rapid diagnostic protocols for antimicrobial susceptibility testing (AST), which is crucial for a timely and rational antibiotic prescription. Here, a recombinant bacteriophage tail fiber protein (TFP) was functionalized on magnetic particles to specifically capture Pseudomonas aeruginosa, while fluorescein isothiocyanate-labeled-magainin II was utilized as the indicator. For solving the magnetic particles’ blocking effects, a reverse assaying protocol based on TFP recognition was developed to investigate the feasibility of detection and AST of P. aeruginosa. P. aeruginosa can be rapidly, sensitively and specifically detected within 1.5 h with a linear range of 1.0 × 102 to 1.0 × 106 colony forming units (CFU)⋅mL−1 and a detection limit of 3.3 × 10 CFU⋅mL−1. Subsequently, AST results, which were consistent with broth dilution results, can be obtained within 3.5 h. Due to the high specificity of the TFP, AST can actually be conducted without the need for bacterial isolation and identification. Based on the proof-of-principle work, the detection and AST of other pathogens can be extended by expressing the TFPs of their bacteriophages.


2021 ◽  
Vol 22 (4) ◽  
pp. 2050
Author(s):  
Lukas Hofmann ◽  
Melanie Hirsch ◽  
Sharon Ruthstein

Thirty-five thousand people die as a result of more than 2.8 million antibiotic-resistant infections in the United States of America per year. Pseudomonas aeruginosa (P. aeruginosa) is classified a serious threat, the second-highest threat category of the U.S. Department of Health and Human Services. Among others, the World Health Organization (WHO) encourages the discovery and development of novel antibiotic classes with new targets and mechanisms of action without cross-resistance to existing classes. To find potential new target sites in pathogenic bacteria, such as P. aeruginosa, it is inevitable to fully understand the molecular mechanism of homeostasis, metabolism, regulation, growth, and resistances thereof. P. aeruginosa maintains a sophisticated copper defense cascade comprising three stages, resembling those of public safety organizations. These stages include copper scavenging, first responder, and second responder. Similar mechanisms are found in numerous pathogens. Here we compare the copper-dependent transcription regulators cueR and copRS of Escherichia coli (E. coli) and P. aeruginosa. Further, phylogenetic analysis and structural modelling of mexPQ-opmE reveal that this efflux pump is unlikely to be involved in the copper export of P. aeruginosa. Altogether, we present current understandings of the copper homeostasis in P. aeruginosa and potential new target sites for antimicrobial agents or a combinatorial drug regimen in the fight against multidrug resistant pathogens.


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